JP5727459B2 - 体内持続性を維持することにより体内半減期が増加したタンパク質またはペプチド融合体 - Google Patents

体内持続性を維持することにより体内半減期が増加したタンパク質またはペプチド融合体 Download PDF

Info

Publication number: JP5727459B2
Authority: JP; Japan
Prior art keywords: alpha; antitrypsin; fusion; α1at; protein
Prior art date: 2009-04-22
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

JP2012505833A

Other languages

English (en)

Japanese (ja)

Other versions

JP2012524062A (ja

Inventor

ヘシンジョン，

スンボムユ，

サンミイ，

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Alteogen Inc

Original Assignee

Alteogen Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2009-04-22

Filing date

2010-04-22

Publication date

2015-06-03

2010-04-22 Application filed by Alteogen Inc filed Critical Alteogen Inc

2012-10-11 Publication of JP2012524062A publication Critical patent/JP2012524062A/ja

2015-06-03 Application granted granted Critical

2015-06-03 Publication of JP5727459B2 publication Critical patent/JP5727459B2/ja

Status Active legal-status Critical Current

2030-04-22 Anticipated expiration legal-status Critical

Links

230000004927 fusion Effects 0.000 title claims description 293
108090000623 proteins and genes Proteins 0.000 title claims description 154
102000004169 proteins and genes Human genes 0.000 title claims description 150
108090000765 processed proteins & peptides Proteins 0.000 title claims description 108
230000002688 persistence Effects 0.000 title claims description 17
102000015395 alpha 1-Antitrypsin Human genes 0.000 claims description 326
229940024142 alpha 1-antitrypsin Drugs 0.000 claims description 323
101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 claims description 293
102000002265 Human Growth Hormone Human genes 0.000 claims description 257
108010000521 Human Growth Hormone Proteins 0.000 claims description 257
239000000854 Human Growth Hormone Substances 0.000 claims description 257
108010050122 alpha 1-Antitrypsin Proteins 0.000 claims description 227
102100022712 Alpha-1-antitrypsin Human genes 0.000 claims description 194
230000004936 stimulating effect Effects 0.000 claims description 79
108010011459 Exenatide Proteins 0.000 claims description 76
150000001413 amino acids Chemical class 0.000 claims description 76
JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims description 76
229960001519 exenatide Drugs 0.000 claims description 76
210000003714 granulocyte Anatomy 0.000 claims description 76
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 75
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 75
230000000694 effects Effects 0.000 claims description 71
102000006992 Interferon-alpha Human genes 0.000 claims description 52
108010047761 Interferon-alpha Proteins 0.000 claims description 52
230000000975 bioactive effect Effects 0.000 claims description 44
238000004519 manufacturing process Methods 0.000 claims description 41
230000035772 mutation Effects 0.000 claims description 24
OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 claims description 21
102000004190 Enzymes Human genes 0.000 claims description 20
108090000790 Enzymes Proteins 0.000 claims description 20
229940088598 enzyme Drugs 0.000 claims description 20
108090000445 Parathyroid hormone Proteins 0.000 claims description 12
108020003175 receptors Proteins 0.000 claims description 12
102000005962 receptors Human genes 0.000 claims description 12
102000004196 processed proteins & peptides Human genes 0.000 claims description 11
108700012941 GNRH1 Proteins 0.000 claims description 10
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims description 10
102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 claims description 10
229940088597 hormone Drugs 0.000 claims description 9
239000005556 hormone Substances 0.000 claims description 9
230000001737 promoting effect Effects 0.000 claims description 9
102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 claims description 8
108010024976 Asparaginase Proteins 0.000 claims description 8
102000011022 Chorionic Gonadotropin Human genes 0.000 claims description 8
108010062540 Chorionic Gonadotropin Proteins 0.000 claims description 8
239000000055 Corticotropin-Releasing Hormone Substances 0.000 claims description 8
102000012289 Corticotropin-Releasing Hormone Human genes 0.000 claims description 8
108010022152 Corticotropin-Releasing Hormone Proteins 0.000 claims description 8
102000003972 Fibroblast growth factor 7 Human genes 0.000 claims description 8
108090000385 Fibroblast growth factor 7 Proteins 0.000 claims description 8
102400000322 Glucagon-like peptide 1 Human genes 0.000 claims description 8
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 8
101800000224 Glucagon-like peptide 1 Proteins 0.000 claims description 8
102000003982 Parathyroid hormone Human genes 0.000 claims description 8
102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 8
108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 8
229940084986 human chorionic gonadotropin Drugs 0.000 claims description 8
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 8
239000000199 parathyroid hormone Substances 0.000 claims description 8
229960001319 parathyroid hormone Drugs 0.000 claims description 8
101710169336 5'-deoxyadenosine deaminase Proteins 0.000 claims description 7
102000055025 Adenosine deaminases Human genes 0.000 claims description 7
102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 7
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 7
102000055006 Calcitonin Human genes 0.000 claims description 6
108060001064 Calcitonin Proteins 0.000 claims description 6
108010017544 Glucosylceramidase Proteins 0.000 claims description 6
229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 6
229960004015 calcitonin Drugs 0.000 claims description 6
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 6
239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 6
108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 5
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 5
239000000556 agonist Substances 0.000 claims description 5
210000003743 erythrocyte Anatomy 0.000 claims description 5
239000012634 fragment Substances 0.000 claims description 5
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
239000000275 Adrenocorticotropic Hormone Substances 0.000 claims description 4
102100026189 Beta-galactosidase Human genes 0.000 claims description 4
108010053652 Butyrylcholinesterase Proteins 0.000 claims description 4
102000012286 Chitinases Human genes 0.000 claims description 4
108010022172 Chitinases Proteins 0.000 claims description 4
102100032404 Cholinesterase Human genes 0.000 claims description 4
102000029816 Collagenase Human genes 0.000 claims description 4
108060005980 Collagenase Proteins 0.000 claims description 4
102400000739 Corticotropin Human genes 0.000 claims description 4
101800000414 Corticotropin Proteins 0.000 claims description 4
108010023321 Factor VII Proteins 0.000 claims description 4
102000012673 Follicle Stimulating Hormone Human genes 0.000 claims description 4
108010079345 Follicle Stimulating Hormone Proteins 0.000 claims description 4
102000008214 Glutamate decarboxylase Human genes 0.000 claims description 4
108091022930 Glutamate decarboxylase Proteins 0.000 claims description 4
239000000095 Growth Hormone-Releasing Hormone Substances 0.000 claims description 4
102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 claims description 4
108010003272 Hyaluronate lyase Proteins 0.000 claims description 4
102000001974 Hyaluronidases Human genes 0.000 claims description 4
102100029199 Iduronate 2-sulfatase Human genes 0.000 claims description 4
101710096421 Iduronate 2-sulfatase Proteins 0.000 claims description 4
102000004627 Iduronidase Human genes 0.000 claims description 4
108010003381 Iduronidase Proteins 0.000 claims description 4
102000004877 Insulin Human genes 0.000 claims description 4
108090001061 Insulin Proteins 0.000 claims description 4
108090000467 Interferon-beta Proteins 0.000 claims description 4
102000003996 Interferon-beta Human genes 0.000 claims description 4
108010074328 Interferon-gamma Proteins 0.000 claims description 4
102000008070 Interferon-gamma Human genes 0.000 claims description 4
102000015696 Interleukins Human genes 0.000 claims description 4
108010063738 Interleukins Proteins 0.000 claims description 4
108010059881 Lactase Proteins 0.000 claims description 4
102000004882 Lipase Human genes 0.000 claims description 4
108090001060 Lipase Proteins 0.000 claims description 4
239000004367 Lipase Substances 0.000 claims description 4
102400000569 Myeloperoxidase Human genes 0.000 claims description 4
108090000235 Myeloperoxidases Proteins 0.000 claims description 4
102000003729 Neprilysin Human genes 0.000 claims description 4
108090000028 Neprilysin Proteins 0.000 claims description 4
102400000050 Oxytocin Human genes 0.000 claims description 4
101800000989 Oxytocin Proteins 0.000 claims description 4
XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 claims description 4
102100036893 Parathyroid hormone Human genes 0.000 claims description 4
101710142969 Somatoliberin Proteins 0.000 claims description 4
102000005157 Somatostatin Human genes 0.000 claims description 4
108010056088 Somatostatin Proteins 0.000 claims description 4
108010023197 Streptokinase Proteins 0.000 claims description 4
102000019197 Superoxide Dismutase Human genes 0.000 claims description 4
108010012715 Superoxide dismutase Proteins 0.000 claims description 4
108010078233 Thymalfasin Proteins 0.000 claims description 4
102400000800 Thymosin alpha-1 Human genes 0.000 claims description 4
108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 4
102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 4
108010092464 Urate Oxidase Proteins 0.000 claims description 4
102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 4
108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 4
230000003213 activating effect Effects 0.000 claims description 4
108010030291 alpha-Galactosidase Proteins 0.000 claims description 4
102000005840 alpha-Galactosidase Human genes 0.000 claims description 4
239000005557 antagonist Substances 0.000 claims description 4
KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical class C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims description 4
108010005774 beta-Galactosidase Proteins 0.000 claims description 4
OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 claims description 4
229960001500 bivalirudin Drugs 0.000 claims description 4
108010055460 bivalirudin Proteins 0.000 claims description 4
210000000988 bone and bone Anatomy 0.000 claims description 4
229960002424 collagenase Drugs 0.000 claims description 4
IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 claims description 4
229960000258 corticotropin Drugs 0.000 claims description 4
229940028334 follicle stimulating hormone Drugs 0.000 claims description 4
229960002773 hyaluronidase Drugs 0.000 claims description 4
108010039650 imiglucerase Proteins 0.000 claims description 4
229960002127 imiglucerase Drugs 0.000 claims description 4
229940125396 insulin Drugs 0.000 claims description 4
229960003130 interferon gamma Drugs 0.000 claims description 4
229960001388 interferon-beta Drugs 0.000 claims description 4
229940116108 lactase Drugs 0.000 claims description 4
235000019421 lipase Nutrition 0.000 claims description 4
210000002540 macrophage Anatomy 0.000 claims description 4
230000000921 morphogenic effect Effects 0.000 claims description 4
229960001723 oxytocin Drugs 0.000 claims description 4
XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 claims description 4
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 claims description 4
229960000553 somatostatin Drugs 0.000 claims description 4
229960005202 streptokinase Drugs 0.000 claims description 4
229960004231 thymalfasin Drugs 0.000 claims description 4
NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 claims description 4
229960000187 tissue plasminogen activator Drugs 0.000 claims description 4
239000003053 toxin Substances 0.000 claims description 4
231100000765 toxin Toxicity 0.000 claims description 4
108700012359 toxins Proteins 0.000 claims description 4
229960005356 urokinase Drugs 0.000 claims description 4
102000004127 Cytokines Human genes 0.000 claims description 3
108090000695 Cytokines Proteins 0.000 claims description 3
230000008512 biological response Effects 0.000 claims description 2
108091008020 response regulators Proteins 0.000 claims description 2
101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 1
235000018102 proteins Nutrition 0.000 description 135
235000001014 amino acid Nutrition 0.000 description 76
229940024606 amino acid Drugs 0.000 description 73
210000004369 blood Anatomy 0.000 description 59
239000008280 blood Substances 0.000 description 59
238000000034 method Methods 0.000 description 48
238000001727 in vivo Methods 0.000 description 38
239000003814 drug Substances 0.000 description 32
239000013598 vector Substances 0.000 description 32
241000700159 Rattus Species 0.000 description 24
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 20
108090000631 Trypsin Proteins 0.000 description 19
102000004142 Trypsin Human genes 0.000 description 19
238000002347 injection Methods 0.000 description 19
239000007924 injection Substances 0.000 description 19
239000012588 trypsin Substances 0.000 description 19
238000002474 experimental method Methods 0.000 description 17
239000000243 solution Substances 0.000 description 16
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 15
210000004027 cell Anatomy 0.000 description 15
239000008103 glucose Substances 0.000 description 15
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 14
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 14
229940079593 drug Drugs 0.000 description 14
229920001223 polyethylene glycol Polymers 0.000 description 14
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 13
229960001230 asparagine Drugs 0.000 description 13
235000009582 asparagine Nutrition 0.000 description 13
239000013604 expression vector Substances 0.000 description 13
229940124597 therapeutic agent Drugs 0.000 description 13
235000018417 cysteine Nutrition 0.000 description 12
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 12
108091008146 restriction endonucleases Proteins 0.000 description 12
238000012453 sprague-dawley rat model Methods 0.000 description 12
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 11
238000003018 immunoassay Methods 0.000 description 11
239000000126 substance Substances 0.000 description 11
230000001225 therapeutic effect Effects 0.000 description 11
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 10
239000004473 Threonine Substances 0.000 description 10
230000002401 inhibitory effect Effects 0.000 description 10
101710081722 Antitrypsin Proteins 0.000 description 9
101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
238000002835 absorbance Methods 0.000 description 9
238000004458 analytical method Methods 0.000 description 9
230000001475 anti-trypsic effect Effects 0.000 description 9
239000013599 cloning vector Substances 0.000 description 9
102000052502 human ELANE Human genes 0.000 description 9
230000003834 intracellular effect Effects 0.000 description 9
239000002773 nucleotide Substances 0.000 description 9
125000003729 nucleotide group Chemical group 0.000 description 9
238000000746 purification Methods 0.000 description 9
210000002966 serum Anatomy 0.000 description 9
239000002753 trypsin inhibitor Substances 0.000 description 9
210000004978 chinese hamster ovary cell Anatomy 0.000 description 8
230000036252 glycation Effects 0.000 description 8
210000000265 leukocyte Anatomy 0.000 description 8
239000008055 phosphate buffer solution Substances 0.000 description 8
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 8
238000013268 sustained release Methods 0.000 description 8
239000012730 sustained-release form Substances 0.000 description 8
108091003079 Bovine Serum Albumin Proteins 0.000 description 7
206010062767 Hypophysitis Diseases 0.000 description 7
238000010171 animal model Methods 0.000 description 7
210000003635 pituitary gland Anatomy 0.000 description 7
230000009467 reduction Effects 0.000 description 7
238000005406 washing Methods 0.000 description 7
102000018997 Growth Hormone Human genes 0.000 description 6
108010051696 Growth Hormone Proteins 0.000 description 6
229960002685 biotin Drugs 0.000 description 6
239000011616 biotin Substances 0.000 description 6
238000003776 cleavage reaction Methods 0.000 description 6
239000012091 fetal bovine serum Substances 0.000 description 6
108020001507 fusion proteins Proteins 0.000 description 6
102000037865 fusion proteins Human genes 0.000 description 6
239000000122 growth hormone Substances 0.000 description 6
230000007017 scission Effects 0.000 description 6
102000003951 Erythropoietin Human genes 0.000 description 5
108090000394 Erythropoietin Proteins 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
238000004820 blood count Methods 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
230000007423 decrease Effects 0.000 description 5
229940105423 erythropoietin Drugs 0.000 description 5
238000007446 glucose tolerance test Methods 0.000 description 5
238000007912 intraperitoneal administration Methods 0.000 description 5
239000011159 matrix material Substances 0.000 description 5
239000002609 medium Substances 0.000 description 5
OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 5
230000008569 process Effects 0.000 description 5
108060003951 Immunoglobulin Proteins 0.000 description 4
108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
239000012980 RPMI-1640 medium Substances 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
125000003275 alpha amino acid group Chemical group 0.000 description 4
239000003242 anti bacterial agent Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
230000008859 change Effects 0.000 description 4
206010012601 diabetes mellitus Diseases 0.000 description 4
230000005847 immunogenicity Effects 0.000 description 4
102000018358 immunoglobulin Human genes 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
239000000758 substrate Substances 0.000 description 4
230000002459 sustained effect Effects 0.000 description 4
108010029961 Filgrastim Proteins 0.000 description 3
102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 3
102000016387 Pancreatic elastase Human genes 0.000 description 3
108010067372 Pancreatic elastase Proteins 0.000 description 3
102000035195 Peptidases Human genes 0.000 description 3
108091005804 Peptidases Proteins 0.000 description 3
102000004338 Transferrin Human genes 0.000 description 3
108090000901 Transferrin Proteins 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
229920002988 biodegradable polymer Polymers 0.000 description 3
239000004621 biodegradable polymer Substances 0.000 description 3
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
238000004925 denaturation Methods 0.000 description 3
230000036425 denaturation Effects 0.000 description 3
238000011161 development Methods 0.000 description 3
239000006167 equilibration buffer Substances 0.000 description 3
229960004177 filgrastim Drugs 0.000 description 3
239000010419 fine particle Substances 0.000 description 3
239000008363 phosphate buffer Substances 0.000 description 3
230000001766 physiological effect Effects 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
229910000162 sodium phosphate Inorganic materials 0.000 description 3
239000001488 sodium phosphate Substances 0.000 description 3
230000001629 suppression Effects 0.000 description 3
239000012581 transferrin Substances 0.000 description 3
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
108700028369 Alleles Proteins 0.000 description 2
239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
229920002873 Polyethylenimine Polymers 0.000 description 2
229920002684 Sepharose Polymers 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
-1 antibodies Proteins 0.000 description 2
230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
210000001185 bone marrow Anatomy 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
108010057085 cytokine receptors Proteins 0.000 description 2
102000003675 cytokine receptors Human genes 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
239000003405 delayed action preparation Substances 0.000 description 2
238000007865 diluting Methods 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
230000001747 exhibiting effect Effects 0.000 description 2
239000008187 granular material Substances 0.000 description 2
230000028993 immune response Effects 0.000 description 2
239000000367 immunologic factor Substances 0.000 description 2
210000003000 inclusion body Anatomy 0.000 description 2
238000001155 isoelectric focusing Methods 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
230000007774 longterm Effects 0.000 description 2
238000010172 mouse model Methods 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 2
108091033319 polynucleotide Proteins 0.000 description 2
239000002157 polynucleotide Substances 0.000 description 2
102000040430 polynucleotide Human genes 0.000 description 2
239000000047 product Substances 0.000 description 2
229940099982 prolastin Drugs 0.000 description 2
230000012743 protein tagging Effects 0.000 description 2
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
230000006798 recombination Effects 0.000 description 2
238000005215 recombination Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
238000010254 subcutaneous injection Methods 0.000 description 2
239000007929 subcutaneous injection Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
238000011282 treatment Methods 0.000 description 2
230000004584 weight gain Effects 0.000 description 2
235000019786 weight gain Nutrition 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 1
101150002595 ALT5 gene Proteins 0.000 description 1
101710126783 Acetyl-hydrolase Proteins 0.000 description 1
102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
101710096214 Alanine aminotransferase 1 Proteins 0.000 description 1
102100033814 Alanine aminotransferase 2 Human genes 0.000 description 1
101710096000 Alanine aminotransferase 2 Proteins 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
101100001521 Alternaria alternata ALT12 gene Proteins 0.000 description 1
101100108689 Alternaria alternata ALT7 gene Proteins 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
108010019673 Darbepoetin alfa Proteins 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
206010014561 Emphysema Diseases 0.000 description 1
108010008165 Etanercept Proteins 0.000 description 1
108091006020 Fc-tagged proteins Proteins 0.000 description 1
206010056438 Growth hormone deficiency Diseases 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 1
101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 1
108091006905 Human Serum Albumin Proteins 0.000 description 1
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
208000026350 Inborn Genetic disease Diseases 0.000 description 1
239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 1
108010028275 Leukocyte Elastase Proteins 0.000 description 1
102000016799 Leukocyte elastase Human genes 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241001529936 Murinae Species 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
102000015731 Peptide Hormones Human genes 0.000 description 1
108010038988 Peptide Hormones Proteins 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000004365 Protease Substances 0.000 description 1
239000012614 Q-Sepharose Substances 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000006978 adaptation Effects 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
230000003321 amplification Effects 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
230000000692 anti-sense effect Effects 0.000 description 1
229940115115 aranesp Drugs 0.000 description 1
SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000012888 bovine serum Substances 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000010367 cloning Methods 0.000 description 1
230000002281 colonystimulating effect Effects 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000003431 cross linking reagent Substances 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000013118 diabetic mouse model Methods 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
229940073621 enbrel Drugs 0.000 description 1
230000029142 excretion Effects 0.000 description 1
208000016361 genetic disease Diseases 0.000 description 1
238000010353 genetic engineering Methods 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
235000009200 high fat diet Nutrition 0.000 description 1
102000044890 human EPO Human genes 0.000 description 1
229920002674 hyaluronan Polymers 0.000 description 1
229960003160 hyaluronic acid Drugs 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
230000008105 immune reaction Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
238000011866 long-term treatment Methods 0.000 description 1
230000004199 lung function Effects 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000000203 mixture Substances 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
230000001817 pituitary effect Effects 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
239000012460 protein solution Substances 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000000611 regression analysis Methods 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
230000007480 spreading Effects 0.000 description 1
238000003892 spreading Methods 0.000 description 1
238000010186 staining Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
- C07K14/8121—Serpins
- C07K14/8125—Alpha-1-antitrypsin
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Life Sciences & Earth Sciences (AREA)
Genetics & Genomics (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Gastroenterology & Hepatology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Medicinal Preparation (AREA)

JP2012505833A 2009-04-22 2010-04-22 体内持続性を維持することにより体内半減期が増加したタンパク質またはペプチド融合体 Active JP5727459B2 (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
KR10-2009-0035190		2009-04-22
KR20090035190		2009-04-22
PCT/KR2010/002520 WO2010123290A2 (ko)	2009-04-22	2010-04-22	체내 지속성을 유지함으로 체내 반감기가 증가된 단백질 또는 펩티드 융합체, 및 이를 이용하여 체내 반감기를 증가시키는 방법

Publications (2)

Publication Number	Publication Date
JP2012524062A JP2012524062A (ja)	2012-10-11
JP5727459B2 true JP5727459B2 (ja)	2015-06-03

Family

ID=43011621

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP2012505833A Active JP5727459B2 (ja)	2009-04-22	2010-04-22	体内持続性を維持することにより体内半減期が増加したタンパク質またはペプチド融合体

Country Status (11)

Country	Link
US (1)	US9012606B2 (ko)
EP (1)	EP2423233B1 (ko)
JP (1)	JP5727459B2 (ko)
KR (1)	KR101183262B1 (ko)
CN (1)	CN102439044B (ko)
AU (1)	AU2010239861B2 (ko)
BR (1)	BRPI1006443B1 (ko)
CA (1)	CA2758445C (ko)
MX (1)	MX2011011130A (ko)
RU (1)	RU2503688C2 (ko)
WO (1)	WO2010123290A2 (ko)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP6216921B2 (ja)	2011-06-24	2017-11-01	ザリージェンツオブザユニバーシティオブコロラド，アボディーコーポレイトＴＨＥＲＥＧＥＮＴＳＯＦＴＨＥＵＮＩＶＥＲＳＩＴＹＯＦＣＯＬＯＲＡＤＯ，ａｂｏｄｙｃｏｒｐｏｒａｔｅ	アルファ−１抗トリプシン融合分子のための組成物、方法および使用
US10400029B2 (en)	2011-06-28	2019-09-03	Inhibrx, Lp	Serpin fusion polypeptides and methods of use thereof
WO2013003641A2 (en)	2011-06-28	2013-01-03	Inhibrx Llc	Serpin fusion polypeptides and methods of use thereof
KR101402702B1 (ko) *	2011-09-15	2014-06-05	(주)알테오젠	신규한 알파-1 안티트립신 변이체, 이의 제조방법 및 용도
US10478508B2 (en)	2012-01-10	2019-11-19	The Regents Of The University Of Colorado, A Body Corporate	Compositions, methods and uses for alpha-1 antitrypsin fusion molecules
US9289507B2 (en)	2012-05-17	2016-03-22	Extend Biosciences, Inc.	Carriers for improved drug delivery
WO2013183948A1 (ko) *	2012-06-05	2013-12-12	씨제이제일제당 (주)	고당화된 지속형 인간 성장호르몬 단백질 및 이의 제조방법
KR101460266B1 (ko) *	2012-06-05	2014-11-11	씨제이헬스케어 주식회사	신규한 지속형 인간 성장호르몬의 정제 방법
KR101504824B1 (ko) *	2013-05-31	2015-03-23	씨제이헬스케어 주식회사	고당화된 지속형 인간 성장호르몬 단백질 및 이의 제조방법
UA116217C2 (uk)	2012-10-09	2018-02-26	Санофі	Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону
KR101516054B1 (ko) *	2012-11-21	2015-05-06	씨제이헬스케어 주식회사	신규한 지속형 인간 성장호르몬 단량체를 제조하는 방법
BR112015014510A2 (pt)	2012-12-21	2017-11-21	Sanofi Sa	agonistas de glp1/gip duais ou de glp1/gip/glucagon trigonais
WO2015086730A1 (en)	2013-12-13	2015-06-18	Sanofi	Non-acylated exendin-4 peptide analogues
TW201609795A (zh)	2013-12-13	2016-03-16	賽諾菲公司	作為雙重ｇｌｐ－１／ｇｉｐ受體促效劑的艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物
GB201322091D0 (en)	2013-12-13	2014-01-29	Cambridge Entpr Ltd	Modified serpins for the treatment of bleeding disorders
EP3080149A1 (en)	2013-12-13	2016-10-19	Sanofi	Dual glp-1/glucagon receptor agonists
WO2015086729A1 (en)	2013-12-13	2015-06-18	Sanofi	Dual glp-1/gip receptor agonists
TW201625669A (zh)	2014-04-07	2016-07-16	賽諾菲公司	衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑
TW201625668A (zh)	2014-04-07	2016-07-16	賽諾菲公司	作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物
TW201625670A (zh)	2014-04-07	2016-07-16	賽諾菲公司	衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑
US9932381B2 (en)	2014-06-18	2018-04-03	Sanofi	Exendin-4 derivatives as selective glucagon receptor agonists
US9789197B2 (en)	2014-10-22	2017-10-17	Extend Biosciences, Inc.	RNAi vitamin D conjugates
EP3220961B1 (en)	2014-10-22	2023-07-05	Extend Biosciences, Inc.	Therapeutic vitamin d conjugates
WO2016065052A1 (en)	2014-10-22	2016-04-28	Extend Biosciences, Inc.	Insulin vitamin d conjugates
WO2016102580A1 (en) *	2014-12-22	2016-06-30	Novo Nordisk A/S	Alpha-1-antitrypsin (a1at) fusion proteins and uses thereof
CN111388680B (zh) *	2015-01-28	2024-01-05	中国科学院天津工业生物技术研究所	一种多肽复合物作为多肽或蛋白质药物载体的应用、方法及其融合蛋白复合物
US10993993B2 (en) *	2015-05-28	2021-05-04	Immunoforge Co., Ltd.	Pharmaceutical composition for treating muscle atrophy or sarcopenia including glucagon-like peptide (GLP-1) or GLP-1 receptor agonist
AR105319A1 (es)	2015-06-05	2017-09-27	Sanofi Sa	Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico
WO2017003270A1 (ko) *	2015-07-02	2017-01-05	주식회사 녹십자	헌터증후군 치료제 및 치료방법
KR20170004814A (ko) *	2015-07-02	2017-01-11	주식회사 녹십자	헌터증후군 치료제
AR105284A1 (es)	2015-07-10	2017-09-20	Sanofi Sa	Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón
PT3348635T (pt) *	2015-09-08	2021-03-15	Japan Chem Res	Novo mutante de albumina do soro humano
WO2018071528A1 (en) *	2016-10-11	2018-04-19	University Of Georgia Research Foundation, Inc.	Proteins and method for treating obesity and associated comorbidities
US11492390B2 (en) *	2017-04-02	2022-11-08	B. G. Negev Technologies And Applications Ltd., At Ben-Gurion University	Mutant alpha-1-antitrypsin compositions and use thereof
KR101964376B1 (ko)	2017-09-29	2019-04-01	주식회사 나이벡	부갑상선호르몬(parathyroid hormone, PTH)에 골조직 선택성 펩타이드가 결합되어 있는 융합 펩타이드를 포함하는 약학 조성물 및 생체재료
KR102167827B1 (ko) *	2017-12-20	2020-10-20	주식회사 알테오젠	신규한 성장 호르몬 수용체 길항제 및 이의 융합 단백질
CN107916257B (zh) *	2018-01-09	2020-07-28	华南理工大学	T1脂肪酶突变体和应用
WO2019222435A1 (en)	2018-05-16	2019-11-21	Halozyme, Inc.	Methods of selecting subjects for combination cancer therapy with a polymer-conjugated soluble ph20
WO2019237079A2 (en) *	2018-06-07	2019-12-12	Xiaolong Zhang	Pharmaceutical composition containing fusion protein and use thereof
WO2020050626A1 (ko) *	2018-09-05	2020-03-12	주식회사 엘지화학	O-글리코실화 가능한 폴리펩타이드 영역을 포함하는 융합 폴리펩타이드
CN114573715A (zh) *	2022-03-14	2022-06-03	江苏雅酶医药科技有限公司	一种重组长效人透明质酸酶及其生产方法和应用
CN117186237A (zh) *	2022-05-29	2023-12-08	中国医学科学院药物研究所	一种含有糜蛋白酶抑制肽的胰岛素杂交肽及其应用

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2601033B1 (fr) *	1986-07-02	1990-01-19	Transgene Sa	Variants de l'alpha-antitryspine humaine glycosylee et procede pour la preparation
US5116964A (en)	1989-02-23	1992-05-26	Genentech, Inc.	Hybrid immunoglobulins
US5605690A (en)	1989-09-05	1997-02-25	Immunex Corporation	Methods of lowering active TNF-α levels in mammals using tumor necrosis factor receptor
US7217689B1 (en)	1989-10-13	2007-05-15	Amgen Inc.	Glycosylation analogs of erythropoietin
FR2686899B1 (fr)	1992-01-31	1995-09-01	Rhone Poulenc Rorer Sa	Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant.
FR2686901A1 (fr)	1992-01-31	1993-08-06	Rhone Poulenc Rorer Sa	Nouveaux polypeptides antithrombotiques, leur preparation et compositions pharmaceutiques les contenant.
KR100239336B1 (ko)	1992-09-29	2000-01-15	구본준	액정 표시 소자
DK0674506T3 (da)	1992-12-02	2001-01-08	Alkermes Inc	Væksthormonholdige mikrosfærer med styret frigivelse
KR100236771B1 (ko)	1997-04-01	2000-02-01	성재갑	히아루론산을 이용한 약물의 서방성 미세입자 제형
US7247704B2 (en) *	2000-12-18	2007-07-24	Arriva Pharmaceuticals, Inc.	Multifunctional protease inhibitors and their use in treatment of disease
US20080095774A1 (en) *	2001-02-16	2008-04-24	Wyeth	Agents and Methods for Specifically Blocking CD28-Mediated Signaling
US7176278B2 (en)	2001-08-30	2007-02-13	Biorexis Technology, Inc.	Modified transferrin fusion proteins
CA2534352A1 (en) *	2003-08-08	2005-02-17	Arriva Pharmaceuticals, Inc.	Methods of protein production in yeast
CN103212084B (zh) *	2003-11-13	2018-07-13	韩美科学株式会社	含有免疫球蛋白fc区作为载体的药物组合物
US8921528B2 (en)	2004-06-01	2014-12-30	Domantis Limited	Bispecific fusion antibodies with enhanced serum half-life
CA2658673A1 (en)	2005-07-27	2008-02-01	Gerald J. Prud'homme	Composition and method for prevention and treatment of type i and type ii diabetes

2010
- 2010-04-22 BR BRPI1006443-5A patent/BRPI1006443B1/pt active IP Right Grant
- 2010-04-22 KR KR1020100037496A patent/KR101183262B1/ko active IP Right Grant
- 2010-04-22 US US13/265,775 patent/US9012606B2/en active Active
- 2010-04-22 RU RU2011147216/10A patent/RU2503688C2/ru active
- 2010-04-22 JP JP2012505833A patent/JP5727459B2/ja active Active
- 2010-04-22 AU AU2010239861A patent/AU2010239861B2/en active Active
- 2010-04-22 CA CA2758445A patent/CA2758445C/en active Active
- 2010-04-22 MX MX2011011130A patent/MX2011011130A/es active IP Right Grant
- 2010-04-22 WO PCT/KR2010/002520 patent/WO2010123290A2/ko active Application Filing
- 2010-04-22 CN CN201080017980.6A patent/CN102439044B/zh active Active
- 2010-04-22 EP EP10767304.8A patent/EP2423233B1/en active Active

Also Published As

Publication number	Publication date
RU2011147216A (ru)	2013-05-27
RU2503688C2 (ru)	2014-01-10
MX2011011130A (es)	2011-11-18
US9012606B2 (en)	2015-04-21
EP2423233A4 (en)	2012-09-26
KR101183262B1 (ko)	2012-09-14
CN102439044A (zh)	2012-05-02
CA2758445A1 (en)	2010-10-28
KR20100116558A (ko)	2010-11-01
JP2012524062A (ja)	2012-10-11
BRPI1006443B1 (pt)	2021-05-25
US20120094356A1 (en)	2012-04-19
AU2010239861A1 (en)	2011-10-27
EP2423233B1 (en)	2015-03-11
BRPI1006443A2 (pt)	2016-09-27
CN102439044B (zh)	2014-08-13
WO2010123290A2 (ko)	2010-10-28
CA2758445C (en)	2016-02-16
AU2010239861B2 (en)	2013-07-11
EP2423233A2 (en)	2012-02-29
WO2010123290A3 (ko)	2011-03-03

Legal Events

Date	Code	Title	Description
2013-09-18	A131	Notification of reasons for refusal	Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130917
2013-12-13	A521	Request for written amendment filed	Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131212
2014-08-06	A131	Notification of reasons for refusal	Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140805
2015-03-19	TRDD	Decision of grant or rejection written
2015-03-25	A01	Written decision to grant a patent or to grant a registration (utility model)	Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150324
2015-04-09	A61	First payment of annual fees (during grant procedure)	Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150402
2015-04-10	R150	Certificate of patent or registration of utility model	Ref document number: 5727459 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150
2018-04-03	R250	Receipt of annual fees	Free format text: JAPANESE INTERMEDIATE CODE: R250
2019-04-02	R250	Receipt of annual fees	Free format text: JAPANESE INTERMEDIATE CODE: R250
2020-04-07	R250	Receipt of annual fees	Free format text: JAPANESE INTERMEDIATE CODE: R250
2021-04-21	R250	Receipt of annual fees	Free format text: JAPANESE INTERMEDIATE CODE: R250
2022-03-08	R250	Receipt of annual fees	Free format text: JAPANESE INTERMEDIATE CODE: R250
2023-03-31	R250	Receipt of annual fees	Free format text: JAPANESE INTERMEDIATE CODE: R250
2024-04-04	R250	Receipt of annual fees	Free format text: JAPANESE INTERMEDIATE CODE: R250

Publication	Publication Date	Title
JP5727459B2 (ja)	2015-06-03	体内持続性を維持することにより体内半減期が増加したタンパク質またはペプチド融合体
CN107759697B (zh)	2023-03-24	制备融合蛋白的方法
JP6689329B2 (ja)	2020-04-28	免疫グロブリンＦｃ変異体
EP2502939B1 (en)	2016-01-27	Nonnatural collagen-like protein and use thereof
CA2607844C (en)	2012-07-10	Pegylated g-csf polypeptides and methods of producing same
CN108743967A (zh)	2018-11-06	含有免疫球蛋白fc区作为载体的药物组合物
CN110339369B (zh)	2024-01-23	制备生理活性多肽复合物的改进方法
CN114846025A (zh)	2022-08-02	超长效胰岛素-Fc融合蛋白及其使用方法
EP3110434B1 (en)	2018-09-19	Uti fusion proteins
KR102136336B1 (ko)	2020-07-22	생리활성 폴리펩타이드 결합체의 고수율 생산을 위한 개선된 제조 방법
EP4089117A1 (en)	2022-11-16	Ph-sensitive fc variant
KR20030094336A (ko)	2003-12-11	인터페론 감마 폴리펩티드 변이체
KR20220041058A (ko)	2022-03-31	pH-감응성 Fc 변이체
EP4047006A1 (en)	2022-08-24	Method for producing fusion protein of serum albumin and growth hormone
US20230015291A1 (en)	2023-01-19	Dnase fusion polypeptides and related compositions and methods
KR20220069610A (ko)	2022-05-27	Fgf19 변이체를 포함하는 신규 융합 단백질 및 이의 용도
EP3307304B1 (en)	2024-05-08	Immunoglobulin fusion proteins and uses thereof